NEWS FROM ESMO

Clinical Update From ESMO: Advanced Melanoma

This Clinical Update is based on information presented during a satellite symposium at the ESMO Congress on 14 September 2008 entitled, “Responding to the Challenge of Advanced Melanoma”. Jeffrey Weber, MD, PhD, from the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida discusses the topic “Enhancing the Anti-Melanoma Activity of T-cells by Targeting the CTLA-4 Receptors,” and this update features highlights from his presentation. The entire program may be viewed as a webcast at www.primeoncology.org.

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) is a negative regulator of T-cell response and can exert a suppressive effect on the immune response against melanoma cells. Two human monoclonal antibodies directed against CTLA-4 have been studied in clinical trials: ipilimumab (an IgG1) which fixes complement and tremelimumab (an IgG2) which does not fix complement. The focus of this update will be ipilimumab (Bristol-Myers Squibb and Medarex).

Ipilimumab has been studied as monotherapy and in combination with vaccines, cytokines (IL-2), and chemotherapy. Significant antitumor activity has been seen in each of these treatment regimens. Side effects seen with inhibition of CTLA-4 are called immune-related adverse events (IRAEs) and are inflammatory in character. The most common of the IRAEs are rash, colitis, and hepatitis, and the occurrence of these events is generally associated with favorable anti-melanoma response. The timing of occurrence of antitumor responses is quite variable. It is important for clinicians to recognize the unique kinetics of response following ipilimumab administration. Indeed, some patients treated with ipilimumab may initially show disease progression followed by either prolonged stable disease or an objective response.

Currently, a phase III registration trial of ipilimumab for first line therapy of metastatic melanoma is ongoing. This trial will randomize 500 treatment naive patients to receive ipilimumab (10 mg/kg q 3 weeks x 4 cycles) + DTIC vs DTIC alone.

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